Efficacy of Prolonged-release Tacrolimus After Conversion From Immediate-release Tacrolimus in Kidney Transplantation: A Retrospective Analysis of Long-term Outcomes From the ADMIRAD Study.

Prolonged-release tacrolimus (PRT) may offer improved outcomes after kidney transplantation compared with immediate-release tacrolimus (IRT). However, data on outcomes beyond 5-y posttransplantation are lacking. Methods: A retrospective, noninterventional chart review study examined long-term graft survival in adult kidney transplant participants in the Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograf to Advagraf (ADMIRAD) clinical trial at 4 Belgian sites. Patients were randomized to receive once-daily PRT or twice-daily IRT for 6 mo, followed by treatment as per real-world clinical practice. Data were collected retrospectively from randomization day until December 31, 2018. Primary endpoints included efficacy failure, defined as a composite endpoint of graft loss, biopsy-confirmed acute rejection, and graft dysfunction. Secondary endpoints included overall patient survival and course of kidney function. Results: This analysis included 78.5% of patients from ADMIRAD (n = 108 PRT; n = 64 IRT). The Kaplan-Meier survival rate without efficacy failure from randomization to year 5 was 0.741 (95% confidence interval [CI]: 0.647, 0.813) for the PRT group (n = 80), and 0.667 (95% CI: 0.536, 0.768) for the IRT group (n = 42) and remained higher for PRT throughout 10 y follow-up (P = 0.041). The Kaplan-Meier estimate of overall survival from the time of last transplant was 0.981 (95% CI: 0.928, 0.995) and 0.880 (95% CI: 0.802, 0.928) at 5 and 10 y in the PRT group. Kidney function parameters and tacrolimus trough levels remained stable over the follow-up period. Conclusions: Patients in the ADMIRAD study who received PRT for up to 10 y had improved long-term outcomes compared with patients receiving IRT, with a consistent effect on both graft and patient survival.

Recurrence and Outcome of Anti-Glomerular Basement Membrane Glomerulonephritis After Kidney Transplantation.

INTRODUCTION: Recurrence of anti-glomerular basement membrane (anti-GBM) glomerulonephritis in the kidney graft is a rare event, described in limited reports. The aim of this study was to evaluate, in a large cohort of patients with long follow-up, the risk of recurrence of anti-GBM disease, the risk factors associated with clinical recurrence, and the long-term patient and graft survival. METHODS: This was a multicenter retrospective study. Inclusion criteria were patients with anti-GBM glomerulonephritis who underwent transplantation of a kidney between 1977 and 2015. Exclusion criteria were systemic vasculitis, lupus erythematosus, and cryoglobulinemia. Recurrence was defined as reappearance of clinical signs of glomerulonephritis along with histological signs of proliferative glomerulonephritis and linear IgG staining on kidney biopsy, with or without anti-GBM antibodies. RESULTS: A total of 53 patients were included. Recurrence of anti-GBM glomerulonephritis in a first kidney transplant occurred in only 1 patient 5 years after transplantation (a prevalence rate of 1.9%) in the context of cessation of immunosuppressive drugs, and resulted in graft loss due to recurrence. Linear IgG staining on kidney biopsy in the absence of histological signs of proliferative glomerulonephritis was observed in 4 patients, in the context of cellular rejection. Patient survival was 100%, 94%, and 89% at 5, 10, and 15 years, respectively. Death-censored first-graft survival rates were 88%, 83%, and 79% at 5, 10, and 15 years, respectively. CONCLUSION: The recurrence rate of anti-GBM glomerulonephritis after transplantation is very low but is associated with graft loss. The long-term patient and graft survival rates are excellent.

Hemodialysis Does Not Induce Detectable Activation of the Contact System of Coagulation.

INTRODUCTION: Systemic anticoagulation is administered during hemodialysis to prevent clotting of the extracorporeal circuit. The role of contact system activation in thrombin generation during hemodialysis using current era dialyzer membranes is unknown. METHODS: We performed a single-center randomized crossover study. Ten patients treated with hemodialysis underwent 3 standardized hemodialysis sessions. For every patient, each session was performed with a different type of dialyzer membrane (polyphenylene [PP], polymethylmetacrylate [PMMA], polyethylenimine-coated polyacrylonitrile [AN69ST]). Blood samples were collected before and 5, 15, 30, 90, and 240 minutes after blood pump start to evaluate coagulation activation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [PF1+2], activated factor XII [FXIIa], kallikrein, activated factor XI [FXIa]). Plasma of healthy volunteers (n = 20) was used as a reference. RESULTS: Baseline TAT and PF1+2 levels were higher in hemodialysis patients compared to healthy controls (median [interquartile range] for TAT: 3.3 [2.9-4.2] vs. 2.4 [2.3-2.5] µg/l [P = 0.0002] and for PF1+2: 647 [478-737] vs. 138 [125-254] pmol/l [P < 0.0002]). Despite the use of systemic anticoagulation, TAT further increased during treatment, with the increase starting after 30 minutes (median TAT at t240: 9.0 µg/l (PP), 5.5 µg/l (PMMA), and 7.2 µg/l (AN69ST), all P < 0.05 vs. baseline). Contact system markers FXIIa and kallikrein did not differ significantly between dialysis patients and healthy controls, whereas baseline FXIa levels were significantly lower in dialysis patients compared to healthy controls (P = 0.001). Levels of all contact system markers remained unchanged during hemodialysis with all types of dialyzer membranes. CONCLUSION: Routine hemodialysis using systemic heparin anticoagulation induces coagulation activation without measurable contact system activation.

Variability in the incidence of renal replacement therapy over time in Western industrialized countries: A retrospective registry analysis.

INTRODUCTION: A growing number of patients started renal replacement therapy (RRT) in Western industrialized countries between 1980 an early 2000s. Thereafter reports from national and international registries suggest a trend towards stabilization and sometimes a decrease in the incidence rate. AIM: To investigate the differences in overall and age-specific incidence rates between industrialized countries from 1998 until 2013. Secondly, to investigate changes in incidence rates over time and their association with specific age categories. METHOD: We extracted the unadjusted overall incidence of RRT and age-specific incidence rates from renal registry reports in Europe, the United States, Canada, Australia and New Zealand. Time trends in the incidence rate by country and age categories were analyzed by Joinpoint regression analysis. RESULTS: The incidence rate in 2013 ranged from 89 per million population (pmp) in Finland to 363 pmp in the US. Incidence rates in the lower age categories (20-64 year) were similar between countries and remained stable over time. Higher incidence countries were characterized by higher numbers of patients in both the 65-74 and ≥75 year categories starting RRT. Joinpoint analysis confirmed that most countries had significant reductions in the incidence rate at the end of the study period. These reductions were explained by lower numbers of older patients starting RRT and were observed also in countries with lower overall incidence rates. CONCLUSION: This study confirmed different incidence rates of RRT between industrialized countries worldwide. Countries with the highest overall incidence rates also had the highest incidence rates in the oldest age categories. Since the early 2000's the number of older patients starting RRT is either stabilizing or even decreasing in most countries. This reduction is universal and is also observed in countries with previously low incidence rates.